Inhibition of dimethylnitrosamine metabolism by some heterocyclic compounds and by substrates and inhibitors of monoamine oxidase in the rat.

Pretreatment of rats with a number of nitrogen-containing heterocyclic compounds was found to inhibit markedly the metabolism of dimethylnitrosamine (DMN) in terms of both CO2 excretion and decline in blood DMN concentration. However, many of these compounds had either much less or no inhibitory effect on the in vivo metabolism to CO2 of a typical mixed-function oxidase substrate, aminopyrine. In addition, a number of model inhibitors of monoamine oxidase (MAO) activity also inhibited DMN metabolism in the intact animal, and a number of primary amines, known substrates of hepatic MAO, inhibited DMN metabolism but not that of aminopyrine in the isolated perfused liver system. These results, together with in vitro data and previously reported studies on the effect of MAO inhibitors and substrates on the mutagenicity of DMN, suggest that the metabolism and bioactivation of DMN may be in part mediated by a MAO type of enzyme activity.